In order to investigate the genetic control of human immune responses, the inheritance of several genes known to play important roles in a variety of immune processes has been analyzed in human families. Probes corresponding to HLA class I, class II (DR alpha, DR beta, DQ alpha, DQ beta, DO alpha and DP beta) and T cell antigen receptor (TcR) alpha chain (C + 3' untranslated region and V4) and beta chain (C and V8.1) genes were used in Southern blotting analyses of DNA samples from the members of eight families. Polymorphic restriction fragments hybridizing with a TcR beta constant (C) region probe were observed to segregate in six of the eight families and certain haplotype assignments could be made. Two additional polymorphisms were observed with a probe corresponding to a variable (V) gene segment and were used to complete assignment of haplotypes for nearly all individuals. Different combinations of the C and two V region markers can result in eight possible distinct haplotypes and all but one of these combinations was observed in the parents of the families studied. While the data regarding segregation of polymorphic V and C fragments provided support for linkage of V and C region gene segments, the diversity of haplotypes at the population level suggests that recombination has occurred between V and C region gene segments and among members of the V region subfamily marked by the probe used. Similar results were obtained using TcR alpha V and C+3' untranslated probes. Human TcR alpha chain haplotypes appears to be quite polymorphic. These polymorphisms will provide useful markers that will facilitate linkage studies, mapping studies, genetic analyses of T cell function, and the means of evaluating the role of TcR genes in disease susceptibility.